Aggrecanases are enzymes that can cleave cartilage aggrecan, a component of the extracellular matrix. Cartilage aggrecan generally includes a core protein with multiple functional domains that allow the cartilage to resist compressive forces. When the degradation of extracellular matrix components exceeds the synthesis of extracellular matrix components, there is a loss of aggrecan and a subsequent disruption of cartilage, resulting in a disruption of the structure and function of certain tissue types. The degradation of aggrecan is believed to be pathophysiological event that is seen in the earlier stages of joint diseases such as osteoarthritis (OA) and rheumatoid arthritis.